An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

Gracida, Xicotencatl; Dion, Michael F.; Harris, Graham P.; Zhang, Yun; Calarco, John A.

doi:10.1016/j.celrep.2017.11.042

Cited by 13 publications

(12 citation statements)

References 75 publications

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“…This likely shows a change in transcriptional priorities and calcium signaling in the simulated cells from cellular metabolic activity signature seen in the unstimulated condition to a more focused genetic signature related to the decoding of external signals. In support of this hypothesis it has recently been demonstrated that the activity of transcription factor Tceb1 is regulated by experience dependent neuronal plasticity driven by specific external stimuli in Caenorhabditis elegans [34]. Tceb1 is a transcriptional regulator of transcription elongation, therefore it has the capacity to be a common regulator of many genes, including calcium signaling genes, which are controlled by neuronal activity firing patterns.…”

Section: Discussionmentioning

confidence: 94%

Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

Iacobaş

Lee

et al. 2019

Genes

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Transcriptional responses to the appropriate temporal pattern of action potential firing are essential for long-term adaption of neuronal properties to the functional activity of neural circuits and environmental experience. However, standard transcriptome analysis methods can be too limited in identifying critical aspects that coordinate temporal coding of action potential firing with transcriptome response. A Pearson correlation analysis was applied to determine how pairs of genes in the mouse dorsal root ganglion (DRG) neurons are coordinately expressed in response to stimulation producing the same number of action potentials by two different temporal patterns. Analysis of 4728 distinct gene-pairs related to calcium signaling, 435,711 pairs of transcription factors, 820 pairs of voltage-gated ion channels, and 86,862 pairs of calcium signaling genes with transcription factors indicated that genes become coordinately activated by distinct action potential firing patterns and this depends on the duration of stimulation. Moreover, a measure of expression variance revealed that the control of transcripts abundances is sensitive to the pattern of stimulation. Thus, action potentials impact intracellular signaling and the transcriptome in dynamic manner that not only alter gene expression levels significantly (as previously reported) but also affects the control of their expression fluctuations and profoundly remodel the transcriptional networks.

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Section: Discussionmentioning

confidence: 94%

Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

Iacobaş

Lee

et al. 2019

Genes

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“…Table S6). In contrast, only 6/119 and 1/119 up-regulated genes were present in the muscle and neuronal TRAP data sets (Gracida et al, 2017), respectively (Fig. 5D, Supp.…”

Section: Gene Expression Is Perturbed In Csr-1a Mutantsmentioning

confidence: 93%

“…Conversely, the genes displaying increased expression showed a weak association with muscle, intestine, and neuronal GO terms (data not shown). To understand which tissues or processes the upregulated genes were associated with, we examined several additional datasets, including modENCODE mRNA-seq data from each stage of development, Translating Ribosome Affinity Purification (TRAP) data from muscles, neurons, and intestines (Gracida et al, 2017), and sperm proteome data (Ma et al, 2014) (Supp. Table S6).…”

Section: Gene Expression Is Perturbed In Csr-1a Mutantsmentioning

confidence: 99%

“…Venn-pie diagrams comparing genes that are differentially expressed in csr-1a(tor159), gfp::3xflag::csr-1b (inner circle) with gene sets that define spermatogenesis-enriched transcripts, oogenesis-enriched transcripts, and gender neutral transcripts (enriched in both spermatogenesis and oogenesis) (Ortiz et al, 2014), and germline expressed sRNAs (as determined by genes that are 2 fold or more depleted of sRNAs in glp-4(bn2) mutants) (Gracida et al, 2017), and the sperm proteome genes (Ma et al, 2014). Numbers in bold indicate statistically significant overlap as calculated by Fisher's Exact Test, p<0.001.…”

Section: Quantification and Statistical Analysismentioning

confidence: 99%

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Two isoforms of the essentialC. elegansArgonaute CSR-1 differentially regulate sperm and oocyte fertility

Charlesworth

Seroussi

Lehrbach

et al. 2020

Preprint

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SUMMARYThe C. elegans genome encodes nineteen functional Argonaute proteins that utilize 22G-RNAs, 26G-RNAs, miRNAs, or piRNAs to regulate their target transcripts. Only one of these proteins is essential under normal laboratory conditions: CSR-1. While CSR-1 has been studied in various developmental and functional contexts, nearly all studies investigating CSR-1 have overlooked the fact that the csr-1 locus encodes two isoforms. These isoforms differ by an additional 163 amino acids present in the N-terminus of CSR-1a. Using CRISPR-Cas9 genome editing to introduce GFP::3xFLAG epitopes into the long (CSR-1a) and short (CSR-1b) isoforms of CSR-1, we identified differential expression patterns for the two isoforms. CSR-1a is expressed specifically during spermatogenesis and in select somatic tissues, including the intestine. In contrast, CSR-1b, is expressed constitutively in the germline. Essential functions of csr-1 described in the literature coincide with CSR-1b. In contrast, CSR-1a plays tissue specific functions during spermatogenesis, where it integrates into a spermatogenesis sRNA regulatory network including ALG-3, ALG-4, and WAGO-10 that is necessary for male fertility. CSR-1a is also required in the intestine for the silencing of repetitive transgenes. Sequencing of small RNAs associated with each CSR-1 isoform reveals that CSR-1a engages with 22G- and 26G-RNAs, while CSR-1b interacts with only 22G-RNAs to regulate distinct groups of germline genes and regulate both sperm and oocyte-mediated fertility.

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“…30 infection. Similarly, exposure to increasing temperatures enhances 5-HT release from the 54 serotonergic neurons (called NSM and ADF neurons) through the activity of the animal's 55 thermosensory neurons (called AFD neurons) and this release of 5-HT cell non-autonomously 56 protects the animal from proteotoxicity (Gracida, Dion, Harris, Zhang, & Calarco, 2017; Iwanir 57 et al, 2016; Shao et al, 2019; Tatum et al, 2015a). However, whether 5-HT released by the 58 parent upon the detection of stress protects germ cells and future progeny from stress is not 59 known.…”

mentioning

confidence: 99%

Serotonin signaling by maternal neurons upon stress ensures progeny survival

Das¹,

Ooi²,

Corchado³

et al. 2020

eLife

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19Germ cells are vulnerable to stress. Therefore, how organisms protect their future progeny from 20 damage in a fluctuating environment is a fundamental question in biology. We show that in 21Caenorhabditis elegans, serotonin released by maternal neurons during stress ensures the 22 viability and stress resilience of future offspring. Serotonin acts through a signal transduction 23 pathway conserved between C. elegans and mammalian cells to enable the transcription factor 24 HSF1 to alter chromatin in soon-to-be fertilized germ cells by recruiting the histone chaperone 25 FACT, displacing histones, and initiating protective gene expression. Without serotonin release 26 by maternal neurons, FACT is not recruited by HSF1 in germ cells, transcription occurs but is 27 delayed, and progeny of stressed C. elegans mothers fail to complete development. These 28 studies uncover a novel mechanism by which stress sensing by neurons is coupled to 29 transcription response times of germ cells to protect future offspring. 30 infection. Similarly, exposure to increasing temperatures enhances 5-HT release from the 54 serotonergic neurons (called NSM and ADF neurons) through the activity of the animal's 55 thermosensory neurons (called AFD neurons) and this release of 5-HT cell non-autonomously 56 protects the animal from proteotoxicity (Gracida, Dion, Harris, Zhang, & Calarco, 2017; Iwanir 57 et al., 2016; Shao et al., 2019; Tatum et al., 2015a). However, whether 5-HT released by the 58 parent upon the detection of stress protects germ cells and future progeny from stress is not 59 known. In fact, mammalian studies are suggestive of the opposite role for elevated levels of 5-60HT that accompany chronic stress in the parent, and increased 5-HT is thought to contribute to 61 behavioral and psychiatric disorders such as schizophrenia, depression, and autism in progeny 62through as yet poorly understood mechanisms (Bonnin et al.unexpected 64 effect given that stress-induced release of 5-HT by neurons and other 5-HT synthesizing cells is 65 a highly conserved phenomenon. 66 67Here we asked whether the stress-induced release of 5-HT by maternal neurons provides any 68 benefits to germ cells and the development of future progeny. We used C. elegans to address this 69 question in an in vivo setting, and cultured mammalian cells to dissect the molecular pathways by 70 which 5-HT might act and to examine the extent to which 5-HT mediated effects are conserved. 71We show that in C. elegans, 5-HT released by maternal neurons upon stress allows the 72 transcription factor heat shock factor 1 (HSF1) to shorten the time to onset of mRNA production 73 in soon-to-be fertilized germ cells. Specifically, 5-HT promotes the post-translational 74 modification of HSF1 by protein kinase A (PKA) allowing HSF1 to recruit the histone chaperone 75 FACT (FAcilitates Chromatin Transcription) and alter histone dynamics to initiate transcription. 76 5 This timely activation of HSF1 in germ cells ensures their viability and future stress tolerance: 77 embry...

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An Elongin-Cullin-SOCS Box Complex Regulates Stress-Induced Serotonergic Neuromodulation

Cited by 13 publications

References 75 publications

Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

Coordinated Activity of Transcriptional Networks Responding to the Pattern of Action Potential Firing in Neurons

Two isoforms of the essentialC. elegansArgonaute CSR-1 differentially regulate sperm and oocyte fertility

Serotonin signaling by maternal neurons upon stress ensures progeny survival

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